Preexisting chronic kidney disease: a potential for improved outcomes from acute kidney injury.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease. In-hospital mortality rate, length of stay, and dialysis dependence were compared in patients with and without a prior history of CKD, defined by an elevated serum creatinine, proteinuria, and/or abnormal renal ultrasound within a year before hospitalization. We hypothesized that patients with AKI and prior history of CKD would have lower mortality rates, shorter lengths of stay, and higher rates of dialysis dependence than patients without prior history of CKD. RESULTS: Patients with AKI and a prior history of CKD were older and underwent nephrology consultation earlier in the course of AKI. In-hospital mortality rate was lower (31 versus 40%, P = 0.04), and median intensive care unit length of stay was 4.6 d shorter (14.7 versus 19.3 d, P = 0.001) in patients with a prior history of CKD. Among dialyzed survivors, patients with prior CKD were also more likely to be dialysis dependent at hospital discharge. Differences in outcome were most evident in patients with lower severity of illness. CONCLUSIONS: Among critically ill patients with AKI, those with prior CKD experience a lower mortality rate but are more likely to be dialysis dependent at hospital discharge. Future studies should determine optimal strategies for managing AKI with and without a prior history of CKD.

Predictors of hyperkalemia risk following hypertension control with aldosterone blockade.

BACKGROUND: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. METHODS: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 + or - 16.2 ml/min/1.73 m(2)) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. RESULTS: The mean age of the patients studied was 64.9 + or - 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 + or - 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of < or = 45 ml/min/1.73 m(2) in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. CONCLUSION: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

The kidney, hypertension, and remaining challenges.

There is an epidemic of chronic kidney disease in the Western world, with hypertension being the second most common cause. Blood pressure control rates, while improving, are still below 50% for the United States population. The following three challenges remain for the treatment of hypertension and associated prevention of end-stage kidney disease. First, a better understanding by the general medical community of how and in whom to use renin angiotensin aldosterone system blockers is needed. Second, the appropriate initiation of fixed-dose combination therapy to achieve blood-pressure goals needs to be clarified. Finally, the subgroup of patients with kidney disease needs more aggressive blood pressure lowering.

The MDRD equation predicts peritoneal dialysis-delivered creatinine clearances from serum creatinine.

BACKGROUND AND OBJECTIVES: The four- and six-variable Modified Diet in Renal Disease equations (MDRDEs) are empiric expressions that estimate GFR in patients with kidney disease. No method currently exists to directly compare MDRDE estimates of clearance by the failing biologic kidney to the clearances achieved by dialytic modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Because the MDRDEs estimate GFR, which in turn determines much of the small molecule clearance by the biologic kidney, the aim of this study was to determine if the MDRDEs would predict the measured creatinine clearances (including residual renal clearance, if any) from the serum creatinine values alone in 454 peritoneal dialysis patients. RESULTS: For the group, the four-variable MDRDE predicted a creatinine clearance of 6.5 +/- 3.7 ml/min/1.73 m(2) when measured clearance was from home collections of dialysate and urine was 6.8 +/- 3.1 ml/min/1.73 m(2). The presence or volume of residual urine had no effect on accuracy. The six-variable MDRDE was similarly accurate. Creatinine appearance rates were similar to those reported in other dialysis populations. CONCLUSIONS: Using serum creatinine values in "standard" fashion, MDRDEs can approximate creatinine clearances achieved by peritoneal dialysis with an accuracy similar to that of the MDRDEs in predialysis populations, perhaps because the MRDREs account exponentially for the increasing fractional gut metabolism of daily creatinine production as the serum creatinine increases. "MDRD-like" equations may provide a much needed method of directly comparing dialytic clearances to those achieved by diseased native kidneys and by kidney transplants.

Emerging therapies for extracorporeal support.

Dialytic therapies have undergone major technological developments in the last decade and emerging techniques are promoted not only for acute kidney injury, but also for sepsis, acute decompensated heart failure, and acute and acute-on-chronic liver failure. New devices specifically target the pathophysiological mechanisms involved in these conditions. In septic shock and sepsis, high-volume hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and high permeability hemofiltration enhance removal of pro-inflammatory mediators, while in liver failure, Molecular Adsorbents recycling System (MARS) and Prometheus favor the elimination of albumin-bound toxins such as bilirubin. In acute decompensated heart failure, simplified ultrafiltration machines are used to reach negative fluid balance in a minimalist setting. In the context of limited resources and growing expansion in the availability of technologies, a critical assessment is required and the use of these devices needs to be put in perspective. This article reviews the mechanisms, advantages and limitations of these techniques along with the current evidence available regarding their influence on major clinical outcomes.

Antihypertensive therapy in the presence of proteinuria.

The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients.

Expanding the definition of hypertension to incorporate global cardiovascular risk.

Recent epidemiologic analyses have changed the way that hypertension is viewed. Cardiovascular risk has been found to be elevated at levels of blood pressure previously believed to be normal and not imparting additional risk. Furthermore, the approach to hypertension has been shifted from viewing and treating it in isolation to a more comprehensive approach that incorporates a focus on global cardiovascular risk and the risk factors commonly associated with having an elevated blood pressure. However, control rates not only for hypertension but also for associated risk factors, such as hyperlipidemia and diabetes, remain abysmal, providing an even greater challenge to providers of care. To change this alarming trend, physicians must become aggressive in using the available armamentarium of lifestyle modifications and drugs in treating hypertension and other risk factors that increase the burden of atherosclerosis.

Microalbuminuria.

Microalbuminuria, originally described more than 3 decades ago as a predictor of nephropathy in patients who had type 1 diabetes mellitus and associated with higher cardiovascular risk, is now linked with increased risk for cardiovascular events rather than progression to end-stage kidney disease. This article reviews the role of microalbuminuria in the context of atherosclerotic vascular disease. It presents the methods for microalbuminuria assessment in clinical practice, its relations with other cardiovascular risk factors, and the pathophysiologic associations between microalbuminuria and vascular damage. In addition, this article discusses the prognostic significance of microalbuminuria for cardiovascular disease as well as existing therapeutic interventions for reducing urine albumin excretion in patients who are at high cardiovascular risk.

Management of hypertension in the cardiometabolic syndrome and diabetes.

This article reviews the goals of antihypertensive therapy in patients with the cardiometabolic syndrome, as well as diabetes in the context of reducing progression of kidney disease and decreasing cardiovascular (CV) mortality. All published guidelines recommend a blood pressure (BP) goal of less than 130/80 mm Hg in people with diabetes. To achieve this BP, an average of three different antihypertensive agents, appropriately dosed, are needed. Initial therapy includes an inhibitor of the renin-angiotensin-aldosterone system usually coupled with a thiazide diuretic. Beta-Blockers are often employed to both lower BP and reduce overall CV risk; however, nondihydropyridine calcium antagonists are comparable in benefit without the adverse metabolic effects. Changing lifestyle patterns to include exercise and proper diet, achieving target BP and lipid goals, and treating with an aspirin daily reduces the absolute risk of a CV event by 20% over less intensive treatment. Thus, treating the cardiometabolic syndrome requires an aggressive approach with a focus on both lifestyle modification and pharmacologic intervention.